MONTREAL, Canada. A landmark multicenter cohort study of patients with systemic lupus erythematosus (SLE) has confirmed a dramatic decrease in relative mortality rates over the last three decades, although patients with lupus still have higher mortality rates than the general population. The researchers, led by Sasha Bernatsky, MD, PhD, report excess mortality in SLE,  particularly among younger women and African Americans. High mortality rates from circulatory disease, renal disease, and infection are of particular concern. The study, published in the August issue of Arthritis & Rheumatism, underlines the need for better prevention and treatment of SLE sequelae and comorbidities, especially cardiovascular disease.¹

"We must assess and treat disease activity aggressively, particularly in its most severe forms, while still aiming to limit the incidence of adverse events due to immune suppressant medications, for instance by prompt recognition of infectious complications," Dr. Bernatsky told CIAOMed. 

Study Included Nearly 10,000 Patients With SLE

The unprecedented size of the study, involving 9457 patients with SLE from 23 centers, was the result of collaboration with the Systemic Lupus International Collaborating Clinics (SLICC) and the Canadian Network for Improved Outcomes in Systemic Lupus (CaNIOS). 

A total of 291 patients died of lupus. Of the 1255 deaths not attributed to lupus the most common cause was circulatory disease, including heart disease, arterial disease, and stroke (n = 460). Cancer, including cancer of the lung and non-Hodgkin's lymphoma, accounted for another 114 deaths; in addition, 64 deaths resulted from infection, including pneumonia.  

High standard mortality rates (SMR) were seen in African-American patients with lupus, in patients under age 40, and in those who had suffered from SLE for less than 1 year. Young adults aged 16 to 24 faced a particularly high relative risk of mortality from infection and renal disorders. Disparities may relate in part to the severity of the disease at presentation. 

"Some patients present initially with very active and life-threatening disease. It is possible that deaths related to SLE activity may occur before the immune-suppressing drugs start to work," Dr. Bernatsky explained.

High doses of corticosteroids and other immune suppressants put the patient at high risk for reactivation of latent infections such as tuberculosis, viral hepatitis, or varicella. "The search continues for more effective and safe drugs as well as for better strategies when using existing drugs, to limit infections and other complications," Dr. Bernatsky said.

Cardiovascular Disease, Cancer Rates High

Though the highest relative mortality rates occurred in the first year of illness, death rates in patients with SLE were much higher over the course of the disease than were those in the general population, with the risk of death from circulatory illnesses failing to decrease appreciably over time. "This may reflect the complex nature of cardiovascular disease in SLE itself or by exposure to medication," Dr. Bernatsky told CIAOMed. "However, doctors should still aim to treat aggressively any modifiable cardiac factors in SLE such as high blood pressure, high cholesterol levels, inactivity, obesity, and smoking."

A further notable finding was the increased risk of death from cancers, including non-Hodgkin's lymphoma and lung cancer. "This is of interest given our recent studies showing a heightened incidence of these types of cancers in SLE," said Dr. Bernatsky. Ongoing research with the SLICC and CaNIOS networks will investigate a possible association between SLE disease activity and lymphoma. 

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Reference

1. Bernatsky S, Boivin J-F, Joseph L, et al. Mortality in systemic lupus erythematosus. Arthritis Rheum. 2006;54:2550-2557.